Abstract：
BACKGROUND: Gerberae Piloselloides Herba (GPH) is derived from Gerbera piloselloides (Linn.) Cass. It is a commonly used traditional medicine in China, featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial and anti-tumor. It is often used as an effective treatment for cough and sore throat as well as bronchial asthma (BA) in China. It was demonstrated in our previous studies that GPH exerted significant effects on the treatment of BA, but its underlying mechanism remains unclear.
OBJECTIVE: This study was aimed at revealing the mechanism through which GPH protects against BA.
METHODS: The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking.
RESULTS: GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking.
CONCLUSIONS: GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.
OBJECTIVE: This study was aimed at revealing the mechanism through which GPH protects against BA.
METHODS: The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking.
RESULTS: GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking.
CONCLUSIONS: GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.
摘要：
背景：非洲菊（GPH）源自非洲菊（Linn。）卡斯。它是中国常用的传统医学，以其特殊的生物活性为特色的镇咳，祛痰药,抗哮喘,抗菌和抗肿瘤。在中国，它通常被用作咳嗽和喉咙痛以及支气管哮喘（BA）的有效治疗方法。我们以前的研究表明，GPH对BA的治疗有显著的影响，但其潜在机制仍不清楚。
目的：本研究旨在揭示GPH对BA的保护机制。
方法:在卵清蛋白诱导的BA小鼠模型中评价GPH对BA的保护作用。通过整合代谢组学和转录组学分析，发现了最关键的途径。通过分子生物学实验和分子对接验证了GPH在调节这些途径中的作用。
结果：GPH具有抗BA作用。在血浆和肺组织中，5和17差异表达的代谢物（DEM），分别,与模型组相比，GPH组有相反的趋势；除γ-氨基丁酸和丁酰肉碱外，这些DEM可能有助于BA诊断。DEM主要参与脂质代谢的调节，其次是葡萄糖代谢和氨基酸代谢。转录组分析表明GPH调节了268个差异表达的基因(DEGs)。代谢组学和转录组学的整合分析表明，GPH可能调节PPAR信号通路，从而影响关键基因靶标如Cyp4a12a的表达，Cyp4a12b,Adh7，Acaa1b和Gpat2；控制脂肪酸降解，不饱和脂肪酸生物合成，甘油磷脂代谢和其他脂质代谢途径；并改善BA。通过逆转录定量聚合酶链反应证实了这种可能性，西方印迹,免疫荧光和分子对接。
结论：发现GPH激活PPAR信号通路，降低Cyp4a12a和Cyp4a12b的水平，并增加Adh7、Acaa1b和Gpat2的水平，从而调节脂质代谢紊乱，减少炎症介质的产生和限制肺损伤。
目的：本研究旨在揭示GPH对BA的保护机制。
方法:在卵清蛋白诱导的BA小鼠模型中评价GPH对BA的保护作用。通过整合代谢组学和转录组学分析，发现了最关键的途径。通过分子生物学实验和分子对接验证了GPH在调节这些途径中的作用。
结果：GPH具有抗BA作用。在血浆和肺组织中，5和17差异表达的代谢物（DEM），分别,与模型组相比，GPH组有相反的趋势；除γ-氨基丁酸和丁酰肉碱外，这些DEM可能有助于BA诊断。DEM主要参与脂质代谢的调节，其次是葡萄糖代谢和氨基酸代谢。转录组分析表明GPH调节了268个差异表达的基因(DEGs)。代谢组学和转录组学的整合分析表明，GPH可能调节PPAR信号通路，从而影响关键基因靶标如Cyp4a12a的表达，Cyp4a12b,Adh7，Acaa1b和Gpat2；控制脂肪酸降解，不饱和脂肪酸生物合成，甘油磷脂代谢和其他脂质代谢途径；并改善BA。通过逆转录定量聚合酶链反应证实了这种可能性，西方印迹,免疫荧光和分子对接。
结论：发现GPH激活PPAR信号通路，降低Cyp4a12a和Cyp4a12b的水平，并增加Adh7、Acaa1b和Gpat2的水平，从而调节脂质代谢紊乱，减少炎症介质的产生和限制肺损伤。
